Vials and other commercially available containers, which are used to hold a drug, a reagent or other pharmaceutically relevant substance and maintain sterility are typically sealed with a septum that is not designed to withstand high positive pressure. In order to transfer a compound or product in such a septum sealed container, it may be necessary for the product to be flushed and pushed through the container in order to obtain a safe and effective infusion into a patient or a receptacle. A two needle system can be used to facilitate the flushing and clearance of the septum sealed container; one needle to push through the flushing fluid and a second needle to exhaust the product and flushing fluid through a transfer tubing into the patient. The transfer tubing from the container to the patient is normally a long catheter with a very small internal diameter. The combination of long length and small diameter creates very large pressure drops from the inlet to the outlet of the catheter. Thus, large back pressures occur in the sealed container due to the pumping force required to move the fluid through the catheter. Leaks in these types of sealed containers can cause a loss of product integrity (especially a loss of sterility, release of dangerous or toxic material and loss of sufficient active ingredient for an effective treatment).
As an example, a flow rate of approximately 1 mL/sec of water flowing through a 1 meter long 3 French catheter requires a pressure drop of approximately 827.4 kPa (120 psig). A 3 French catheter has an outer diameter of 1 mm, and an inner diameter of approximately 0.6 mm. A 1 mL/sec flow rate is moderate yet this magnitude of pressure (827.4 kPa; 120 psig) is very high and a septum seal is not typically designed to withstand such pressures.
There is therefore a need for a method of improving septum resistance to such high pressures in cases where it is difficult to withdraw the product safely or effectively from the original container (as is the case with therapeutic microspheres such as THERASPHERE® Y-90 glass microspheres or SIR-SPHERES® Y-90 resin microspheres). There can be other applications where high leakage resistance is desirable, such as mixing or rinsing after the addition of a chemical reagent to a substrate inside a septum sealed container. Such an application could include adding an active ingredient to initially inactivated microspheres, which in turn could include both a mixing and a rinsing step.